Mitochondria-targeting natural product rhein conjugated with dichloroacetate as the dual inhibitor of glycolysis and oxidative phosphorylation to off energize cancer cells and induce ROS storm DOI Creative Commons
Zhili Zhang, Shiming Tang, Ming‐Hui Qi

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(11), P. 4909 - 4929

Published: March 31, 2025

Rationale: Metabolic reprogramming emerges as a remarkable hallmark of cancer cells and exhibits potential in the development metabolic modulators. Numerous small-molecule inhibitors mainly target reversing dominant-glycolysis pathway. However, energy adaptation that facilitates alternation phenotypes from glycolysis to oxidative phosphorylation (OXPHOS) undermines treatment efficacy. Thus, small molecular therapeutic agents, concurrently cutting off cellular metabolism OXPHOS trigger stress damage, hold promise for therapy. Methods: Herein, natural product rhein with capacity mitochondria-targeting was conjugated pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) form multifunction molecule drug Rhein-DCA conjugate. The ATP production inhibition, damage antitumor efficacy conjugate were evaluated both vitro vivo. Results: Rhein unit not only led effective accumulation mitochondria, but also promoted binding DCA PDK1, enhancing typical inhibition by via PDK-PDH axis. Unlike classical PDK inhibitors, which restrained restored OXPHOS, within further suppressed mitochondrial respiratory chain complex induced sustained opening permeability transition pore, destroying intractable OXPHOS. Importantly, component elevated reactive oxygen species (ROS) level disrupt thus ROS triggered release associated patterns. Simultaneously, weakened lactate-mediated immunosuppression reducing lactate levels tumor microenvironment. Eventually, polarization state tumor-associated macrophages could be effectively reversed following oral administration. Conclusion: This study designed dual-inhibitor circumvent adaptations simultaneously induce immunogenic cell death repolarization, thereby synergistically promoting

Language: Английский

Mechanistic insights into the role of traditional Chinese medicine in treating gastric cancer DOI Creative Commons
Ziqiang Chen, Ting Yu, Yunhe Wang

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 21, 2025

Gastric cancer remains a leading cause of cancer-related mortality worldwide, with advanced stages presenting significant challenges due to metastasis and drug resistance. Traditional Chinese Medicine (TCM) offers promising complementary approach characterized by holistic treatment principles minimal side effects. This review comprehensively explores the multifaceted mechanisms which TCM addresses gastric cancer. Specifically, we detail how inhibits aerobic glycolysis downregulating key glycolytic enzymes metabolic pathways, thereby reducing energy supply essential for cell proliferation. We examine suppresses angiogenesis targeting vascular endothelial growth factor (VEGF) cyclooxygenase-2 (COX-2) effectively starving tumors nutrients oxygen required metastasis. Furthermore, modulates immune microenvironment enhancing activity effector cells such as CD4 + CD8 T natural killer (NK) while immunosuppressive like regulatory (Tregs) myeloid-derived suppressor (MDSCs). These actions collectively contribute slowing tumor progression, inhibiting metastasis, body’s antitumor response. The insights presented underscore potential an integral component comprehensive strategies, highlighting avenues future research clinical application improve patient outcomes.

Language: Английский

Citations

0
Intranuclear TCA and mitochondrial overload: the nascent sprout of tumors metabolism DOI

Weixi Yuan,

Guozhong Lu, Yin Zhao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217527 - 217527

Published: Feb. 1, 2025

Language: Английский

Citations

0
Ldha Accelerates Primary Cisplatin Resistance in Lung Adenocarcinoma by Modulating Ambra1 Ubiquitination Via Moonlighting Functions DOI
Fengguo Xu, Qiang Wang, Ying Zhang

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
HSP90 co-regulates the formation and nuclear distribution of the glycolytic output complex to promote resistance and poor prognosis in gastric cancer patients DOI Creative Commons

Gaigai Shen,

Shiya Liu,

Yuanting Cao

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 10, 2025

Resistance to treatment is a critical factor contributing poor prognosis in gastric cancer patients. HSP90 has emerged as promising therapeutic target; however, its role regulating tumor metabolic pathways, particularly glycolysis, remains poorly understood, which limits clinical application. We identified proteins that directly interact with using immunoprecipitation (IP) followed by mass spectrometry. The relationship between and glycolysis was further investigated through transcriptomic analyses vitro experiments. Mechanistic insights were obtained spectrometry, co-immunoprecipitation (Co-IP) assays, drug sensitivity tests, bioinformatics analyses. Additionally, we developed scoring system based on data evaluate prognostic significance association resistance Our multi-omics studies revealed regulates influences the stemness properties of cells. Mechanistically, facilitates assembly glycolytic multi-enzyme complex, termed HGEO enhances metabolism. formation multienzyme complex comprising key enzymes including PGK1, PKM2, ENO1, LDHA, thereby facilitating production final products. refer this "HSP90-Glycolytic Output Complex" (HGEO Complex). quantified phenomenon (HGScore), finding patients high HGScore exhibited more malignant signatures, increased treatment, poorer prognoses. Furthermore, demonstrated localized nucleus, regulated nuclear lamina protein LMNA, contributes adverse outcomes. In experiments indicated inhibiting sensitizes cells chemotherapy. findings suggest LMNA mediated localization enhancing traits mechanisms cancer. Targeting pathway may offer novel strategy improve

Language: Английский

Citations

0
Huachansu suppresses colorectal cancer via inhibiting PI3K/AKT and glycolysis signaling pathways: Systems biology and network pharmacology DOI

Hongxuan YANG,

Yixu Chen,

Chun-Lan Dai

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119479 - 119479

Published: Feb. 1, 2025

Language: Английский

Citations

0
Transplantation of gastric epithelial mitochondria into human gastric cancer cells inhibits tumor growth and enhances chemosensitivity by reducing cancer stemness and modulating gastric cancer metabolism DOI Creative Commons
Hsin‐Yi Tsai,

Kuen-Jang Tsai,

Deng-Chyang Wu

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 23, 2025

Language: Английский

Citations

0
Study on the Mechanism of Jieduquyuziyin prescription Improving the Condition of MRL/lpr Mice by Regulating T Cell Metabolic Reprogramming through the AMPK/mTOR Pathway DOI
Qingmiao Zhu, Yaxue Han, Xiaolong Li

et al.

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: 345, P. 119584 - 119584

Published: March 3, 2025

Language: Английский

Citations

0
Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies DOI Creative Commons
Jinshou Yang,

Feihan Zhou,

Xiyuan Luo

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 3, 2025

Abstract Transcriptional dysregulation is a hallmark of cancer initiation and progression, driven by genetic epigenetic alterations. Enhancer reprogramming has emerged as pivotal driver carcinogenesis, with cells often relying on aberrant transcriptional programs. The advent high-throughput sequencing technologies provided critical insights into enhancer events their role in malignancy. While targeting enhancers presents promising therapeutic strategy, significant challenges remain. These include the off-target effects enhancer-targeting technologies, complexity redundancy networks, dynamic nature reprogramming, which may contribute to resistance. This review comprehensively encapsulates structural attributes enhancers, delineates mechanisms underlying malignant transformation, evaluates opportunities limitations associated cancer.

Language: Английский

Citations

0
Targeted mitochondrial therapy for pancreatic cancer DOI
Xinya Zhao, Guoyu Wu,

Xufeng Tao

et al.

Translational Oncology, Journal Year: 2025, Volume and Issue: 54, P. 102340 - 102340

Published: March 5, 2025

Language: Английский

Citations

0
Metabolic reprogramming in cancer and senescence DOI Creative Commons
Yuzhu Zhang, J. Tang, Can Jiang

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 1, 2025

The rising trend in global cancer incidence has caused widespread concern, one of the main reasons being aging population. Statistical data show that and mortality rates a clear upward with age. Although there is commonality between dysregulated nutrient sensing, which features aging, metabolic reprogramming tumor cells, specific regulatory relationship not clear. This manuscript intends to comprehensively analyze senescence reprogramming; as well reveal impact key factors leading cellular on tumorigenesis. In addition, this review summarizes current intervention strategies targeting sensing pathways, clinical cases treating tumors characteristics existing nanodelivery research strategies. Finally, it also suggests sensible dietary habits for those who wish combat aging. conclusion, attempts sort out link metabolism provide new ideas treatment.

Language: Английский

Citations

0